The majority of
hepatocellular carcinomas arise in background chronic
liver disease, particularly
cirrhosis. The pathogenesis of noncirrhotic
hepatocellular carcinomas remains unclear. While malignant transformation reportedly occurs in <15% of
hepatocellular adenoma, the prevalence of noncirrhotic
hepatocellular carcinomas arising from a pre-existing
adenoma is a challenge to study. Cirrhotic
hepatocellular carcinoma and
hepatocellular adenoma may be subclassified by molecular pathways, but little is known in noncirrhotic
hepatocellular carcinoma. We aim to delineate clinical, morphologic and immunohistochemical features of noncirrhotic
hepatocellular carcinoma to evaluate for possible derivation from
hepatocellular adenoma. We evaluated the clinicopathologic features of 74 noncirrhotic
hepatocellular carcinomas from 72 patients for underlying clinical conditions and immunohistochemical markers known to be associated with
hepatocellular adenoma. Men were more commonly affected (59%); however, in the <50-year-old group, women predominated (8:1). The age range was wide: 18-83 years; median-64 years. Underlying
liver diseases were identified in only 7%; however, 25% had
diabetes mellitus, 69% were
overweight or obese and 58% had
metabolic syndrome. Only 50% of the noncirrhotic
hepatocellular carcinoma were encapsulated. As published in
hepatocellular adenoma, multifocality and larger
tumor size were more common in
liver fatty acid-binding protein-negative noncirrhotic
hepatocellular carcinoma.
Beta-catenin nuclear positivity was uncommon (5%), and was restricted to
hepatocellular carcinomas in older men.
Serum amyloid A positivity was not restricted to any subtype. In summary, we present the largest series to date examining noncirrhotic
hepatocellular carcinoma. We evaluated these with current
hepatocellular adenoma subclassification markers for possible associations. Thirty percent of the 74 noncirrhotic
hepatocellular carcinoma had some clinical, morphological or immunophenotypical associations currently described in
hepatocellular adenoma. Our data also confirm the association of noncirrhotic
hepatocellular carcinoma in middle-aged to elderly men, an association with
metabolic syndrome, and, as with
hepatocellular adenoma, that women predominated in the noncirrhotic
hepatocellular carcinoma subjects <50 years of age.